Encephalopathy is a large category of disease with any brain organic injury, cerebral neuron tissue injury caused by heredity, congenital atelencephalia, cerebral trauma, cerebral tumor, cerebral hemorrhage, cerebral infarction, infection, poisoning by chemical drugs, and so on, which cause symptom and physical sign of patients' hypophrenia, thought and language obstacle, sense abnormity, hemiplegia and even incontinence, and so on. Common encephalopathy can be divided into three categories: the first is infantile brain paralysis, hypophrenia etc. caused by genetic, congenital hypogenesis; the second is acute cerebral injury sequela caused by trauma, and cerebral apoplexy sequela caused by cerebrovascular disease, etc; the third is chronic degenerative disease of cerebral neuron aging degradation caused by central nerve fiber injury, including Alzheimer's disease, brain atrophy, Parkinson's disease, etc.
For all sorts of encephalopathy, it is the pathological nature of encephalopathy that results in losing the function of brain neuron, which is the blockage of neural information transmission channel (brain road)—nerve fiber interferes the conduction of diversified nerve information. For example, stroke is a damage, fracture, jam of nerve fiber conduction function, due to cerebral vascular blockage or rupture, which again causes neuron degeneration, injury or death, the emerging hemiplegia, aphasia and other dysfunction of sensory, movement. Another example is that if fetal brain nerve fiber development is blocked, neuronal cell differentiation and maturation cannot be promoted, and newborns is ischemic, hypoxic, resulting in cerebral palsy of central movement dysfunctions mainly. Another example is that Parkinson's disease is caused by decrease of the number of brain substantia neuron, and deficiency of dopamine synthesis; the senescence and apoptosis of the information transmission channels on the nerve fibers are exacerbated, causing the aging of brain cells (brain atrophy) and finally, senile dementia.
Encephalopathy is a more and more serious threat to human health, and also one of the hot issues concerned in present society, medical community. According to the survey, the number of cerebral infarction, cerebral hemorrhage, cerebral atrophy in dementia, infantile cerebral palsy, epilepsy, Parkinson's disease, traumatic brain injury, brain nerve injury diseases account for about 30% of the total number of human disease. And cerebral infarction, cerebral hemorrhage, etc have four-high characters of high incidence, high mortality, high disability rate, high recurrence rate. The annual number of new encephalopathy patients is about 10 million cases in China, the mortality rate is about 75%, the medical expenses on the treatment of encephalopathy in country and family amounts to hundreds of billion Yuan.
Cerebral vascular diseases are divided by arterial injury into: cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, hypertensive encephalopathy and other types of arterial diseases. Cerebral vascular disease divided by vein injury is mainly intracranial venous system thrombosis, and the most common is cerebral infarction, cerebral hemorrhage. Cerebral hemorrhage is the intracerebral hemorrhage caused by the rupture of cerebral arterial, venous or capillary, which account for about 20% to 30% of all the cerebral vascular disease.
Stroke also called apoplexy or cerebrovascular accident, is acute localized, transient or permanent brain damage caused by ischemia or hemorrhage, usually including a group of diseases containing cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, which is in top 3 reason of human death and the first reason of disabling. According to the Ministry of health survey, annual stroke rate is 150 per 100 thousand, fatality rate is 120 per 100 thousand in China, the existing number of stroke patients is about 5 to 6 million, in which about 75% of the people loss working ability in different degrees, severe disabled people accounts for more than 40%. With the aging of the population, stroke problem will become more serious, society and economy will be overwhelmed. The ischemic stroke accounts for 43%-65% of the acute cerebral vascular disease, the fatality rate is 15%-25%, it is a problem hard to be resolved in our medical community.
At present, more and more domestic and international reports point out the importance of early treatment of ischemic cerebral vascular disease, especially within 3 to 6 hours after onset. The research results of tPA thrombolysis of USA NINDS (within 3 hours after onset) show that the number of patient whose neural function recover to normal increase by 11% compared to the control group, but within 36 hours the intracranial hemorrhage of treatment group is increased significantly (6.4% vs 0.6%). Due to thrombolytic therapy is still in initial research phase with early high hemorrhage rate, the risk/efficacy ratio needs to be defined. Anticoagulant therapy (including heparin and peroral anticoagulants) has been used for preventing from thromboembolism expansion and progressive cerebral vascular disease, transient cerebral ischemic attack, vertebral—basilar artery thrombosis and preventing from cerebral thromboembolism recurrence for a long time, the efficacy remains uncertain, if it is improperly used, the risk of intracranial and systemic hemorrhage is increased. The research reports of large randomized, controlled, double-blind on defibringen treatment is not many, and is still in the research stage. The problems of what extent the defibringen is, how to reduce hemorrhage complications, remain to be solved, and the efficacy has to be further evaluation yet.
In the interventional therapy, according to the report, carotid endarterectomy has made a certain effect for prevention and cure of transient cerebral ischemic attack, the curative effect is good relatively for the patient whose internal carotid artery occlusion is more than 70%. Although these interventional therapy has attracted more and more attention, but information including that of intracranial and extracranial vascular percutaneous transluminal angioplasty intravascular stent implantation or combined with thrombolytic therapy is little, which is still in research stage, lacking of mature experience.
Cerebral protective agent is a hotspot of current research, it has certain basis in theoretic, but from now on, the preparation with determinate effective by clinical study has not found yet.
In conclusion, there has been no big breakthrough in the treatment of acute ischemic cerebrovascular disease from now on. Although there are many methods within which some are still in study stage, but the efficacy is not very sure yet. There is an urgent need to develop a new medicine with good efficiency, little toxic effect, novel chemical structure, capability of treating cerebrovascular disease in clinic, and it is helpful to understand the cerebral vascular disease pathophysiology process deeply.
Craniocerebral trauma is in the second place of incidence rate of systemic trauma, but the mortality and morbidity rank the first. Our Country has about 600000 of traumatic brain injury patients every year, in which about 100000 people died. Craniocerebral trauma has become the most important injury lethal factor of children and young people in developed country. Craniocerebral trauma patients usually present with loss of consciousness, motor nerve dysfunction, memory impairment and mental dysfunction. In order to save the lives of patients, improve their living state, clinicians often use a variety of cerebral protection medicine, hoping to promote the recovery of the patients' brain function. But based on “Chinese craniocerebral trauma patients of cerebral protection medication guide” which is first issued in 2008 by the Chinese Medical Association of neurosurgeons branch, neurological trauma experts committee of China, the clinical curative effect of some common-used drugs is poor, and some drugs are even harmful.
Except the rescue time has to be fast, the more important for treatment of Craniocerebral trauma patients is how to use effective protection drugs rationalized, standardized. The therapeutic levels of craniocerebral trauma are very different between hospitals at present in our country, the therapeutic method is not standardized and rational, it is different in understanding too. Since a long term, there have been a large number of so-called cerebral protection drugs in clinic, it is blindfold to choose and use those drugs. The foreign scholars have adopted evidence-based medicine method, more than 200 categories of brain protection drugs are used in the treatment of acute craniocerebral trauma patients, but failed to find any category of drug with big clinical effects. While some foreign authoritative medical journal, such as “Lancet”, “new England medicine”, on which the latest research findings are published about those medical drugs is also disappointing: such as, the international multicenter found that a large dose hormone can increase the mortality of patients through more than 10000 cases of evidence-based medicine study; the research reports of 7 medical centers of USA show that magnesium sulfate is ineffective on acute craniocerebral trauma patients, and even harmful; albumin is a drug in common usage in clinical treatment of acute craniocerebral trauma brain edema, but it might be harmful to use for inappropriate long-term and large doses; a large sample research of 35 hospitals in 13 countries found that nimodipine, one of the calcium antagonists, has no therapeutic effect on traumatic subarachnoid subarachnoid hemorrhage.
According to research results above, combined with China's basic national conditions and the actual situation of clinical diagnosis, “therapeutic guidelines of brain protection drugs for China craniocerebral trauma patients” presents opinions about 10 categories of drugs as follows: do not recommend strongly on using a large dose hormone, magnesium and super large amounts of albumin; and use conventional dose according to pharmacopoeia. Do not recommend on using nimodipine, glutamate receptor antagonists, free radical scavengers, bradykinin antagonists and mitochondrial function protection agent. Recommend on using cautiously a variety of peptide brain nerve nutrition drugs, whose curative effect on craniocerebral trauma patients lack the first-class clinical evidence of evidence-based medicine. Recommend on the using ATP, coenzyme A, vitamin B6 and vitamin C, which has no adverse reaction attested by long-term clinical application, and prices are cheaper, pharmacological effects are clear.
Therefore, there is a great need of a new cerebral protective medicine in clinic.